In-situ solvent recycling process for solid phase peptide synthesis at elevated temperatures

Abstract

An improvement of deprotection in solid phase peptide synthesis is disclosed. The method includes the steps of adding the deprotection composition in high concentration and small volume to the mixture of the coupling solution, the growing peptide chain, and any excess activated amino acid from the preceding coupling cycle; and without any draining step between the coupling step of the previous cycle and the addition of the deprotection composition for the successive cycle; and with the coupling solution at a temperature of at least 30° C.

The invention claimed is: 
     
       1. A method of deprotection in batch solid phase peptide synthesis in which the improvement comprises:
 adding a base deprotection composition to a mixture of a coupling solution, a growing peptide chain, and any excess activated amino acid from a preceding coupling step; 
 wherein the deprotection composition has a concentration of at least 50% base by volume and is added to the mixture of the coupling solution, the growing peptide chain, and any excess activated amino acid from the preceding coupling step in an amount that is less than ⅓ of the volume of the coupling solution; 
 without any draining step between the coupling step of the preceding coupling cycle and the addition of the deprotection composition for the successive cycle; and 
 with the coupling solution at least 30° C. 
 
     
     
       2. A method according to  claim 1  wherein the deprotection composition is an organic base. 
     
     
       3. A method according to  claim 1  using Fmoc solid phase peptide chemistry. 
     
     
       4. A method of deprotection in batch solid phase peptide synthesis in which the improvement comprises:
 adding a base deprotection composition to a mixture of a coupling solution, a growing peptide chain, and any excess activated amino acid from the preceding coupling cycle step; 
 wherein the deprotection composition is added to the mixture of the coupling solution, the growing peptide chain, and any excess activated amino acid from the preceding coupling step in a concentration of at least 50% base by volume and an amount that is less than ⅓ of the volume of the coupling solution; 
 without any draining step between the coupling step of the preceding coupling cycle and the addition of the deprotection composition for the successive cycle which removes at least 50% of the volume of the preceding coupling cycle coupling solution; and 
 with the coupling solution at a temperature of at least 30° C. 
 
     
     
       5. A method according to  claim 4  wherein the deprotection composition is an organic base. 
     
     
       6. A method according to  claim 4  using Fmoc solid phase peptide chemistry.